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A Phase I Trial of Bevacizumab and Temsirolimus in Patients With Advanced Malignancy


Phase 1
N/A
N/A
Open (Enrolling)
Both
Advanced Cancer

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Trial Information

A Phase I Trial of Bevacizumab and Temsirolimus in Patients With Advanced Malignancy


The Study Drugs:

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels that supply nutrients necessary for tumor growth.

Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells
to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of bevacizumab and temsirolimus combined, based on when you joined this study. Up to
13 dose levels of the study drug combination will be tested. Three (3) participants will be
enrolled at each dose level. The first group of participants will receive the lowest dose
level. Each new group will receive a higher dose than the group before it, if no
intolerable side effects were seen. This will continue until the highest tolerable dose of
the study drug combination is found.

If you choose to enroll in the expansion group of patients being treated at the highest
tolerable dose of the study drug combination found, you will be required to undergo added
testing, as follows:

- You will have additional blood drawn (about 2 teaspoons each time) during Cycle 1. This
blood will be drawn before you begin taking the study drugs; on Day 1 at about 1, 4, 8,
and 24 hours after the start of your first infusion; at Day 8 of Cycle 1; at Day 15 of
Cycle 1; and at the end of Cycle 1. The blood will be used to see how the study drug
combination acts in the body and to learn its effect on cancer cells.

- You will have 2 tumor biopsies performed. These samples will be used to see how the
study drug combination acts in the body and to learn its effect on cancer cells. These
tumor biopsies will be performed during the screening visit and at the end of Cycle 1.
To perform a tumor biopsy, the affected area is numbed with anesthetic and some or all
of the tumor tissue is removed with a small knife.

- You will have extra imaging scans performed and used to see how the study drug
combination may be affecting blood vessels that supply nutrients and oxygen to cancer.
A DCE-MRI scan will be performed during the screening visit, at 24-48 hours after the
start of Cycle 1, and at the end of Cycle 1. Like a regular MRI scan, the DCE-MRI scan
involves passing part or all of the body into a long, narrow tube scanner that is open
at both ends.

Study Drug Administration:

Bevacizumab and temsirolimus will be given in "cycles." Cycles will be about 21 days long
or longer, depending on any side effects you may experience.

Bevacizumab is given by vein on Day 1 of each cycle. On Day 1 of Cycle 1, you will receive
it over 90 minutes. If you tolerate it well in Cycle 1, you will receive it over 60 minutes
in Cycle 2. If you tolerate it well in Cycle 2, you will receive it over 30 minutes in
Cycle 3. It will continue to be given over 30 minutes in Cycle 4 and further cycles, as
long as you still tolerate it well. Also, if the first dose is well tolerated, you may be
given the remaining doses of Bevacizumab in the doctor's office in or near your hometown.

Temsirolimus is given by vein on Days 1, 8, and 15 of each cycle. During Day 1 of Cycle 1,
you will receive it over 60 minutes. If you tolerate it well on Day 1 of Cycle 1, it will
be given over 30 minutes on Days 8 and 15 of Cycle 1 and over 30 minutes in further cycles,
as long you still tolerate it well. Also, if the first dose is well tolerated, you may be
given the remaining doses of Temsirolimus in the doctor's office in or near your hometown.

Study Visits:

You will have a physical exam and blood drawn (about 1 tablespoon each time) for routine
tests once between Days 7 and 14 during Cycle 1. During the rest of the cycles, you will
have a physical exam and blood drawn (about 1 tablespoon each time) for routine tests once
every 3 weeks. The status of the disease will be checked by a CT or MRI scan after every 2
cycles, starting after Cycle 2.

Length of Study Participation:

You may continue to receive additional cycles of the study drugs, unless the cancer gets
worse or intolerable side effects occur. In that case, you will be taken off study.

Once your participation is over in this study, you will receive standard-of-care follow-up
for the disease.

This is an investigational study. Bevacizumab and temsirolimus are commercially available.
Bevacizumab is FDA approved for the treatment of colorectal cancer and a type of lung
cancer. Temsirolimus is FDA approved for the treatment of kidney cancer that has spread.
The combination of bevacizumab and temsirolimus is not FDA approved. At this time, it is
being used in research only.

Up to 183 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients with advanced or metastatic cancer that is refractory to standard therapy,
relapsed after standard therapy, or have no standard therapy that induces a CR rate
of at least 10% or improves survival by at least three months.

2. Patients should be at least four weeks from the last day of therapeutic radiation or
cytotoxic chemotherapy or from antibody therapy, or at least five half-lives from
non-cytotoxic targeted or biologic therapy. Patients may have received palliative
radiation immediately before (or during) treatment provided radiation is not to the
only target lesion available.

3. ECOG performance status /= 60%).

4. Patients must have allowable organ and marrow function defined as: absolute
neutrophil count >/= 1,000/mL; platelets >/=50,000/mL; creatinine bilirubin cholesterol of no more than 350mg/dL; triglyceride level of no more than 400mg/dL.

5. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 90 days after the last dose.

6. Ability to understand and the willingness to sign a written informed consent document

7. Patients may not be receiving any other investigational agents and/or any other
concurrent anticancer agents or therapies.

Exclusion Criteria:

1. Patients with hemoptysis within 28 days prior to entering the study.

2. Patients with clinically significant unexplained bleeding within 28 days prior to
entering the study

3. Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg,
diastolic blood pressure > 90 mmHg on medication).

4. Patients with clinically significant cardiovascular disease: - History of CVA within
6 months - Myocardial infarction or unstable angina within 6 months - Unstable angina
pectoris

5. Pregnant or lactating women.

6. History of hypersensitivity to bevacizumab, murine products, or any component of the
formulation.

7. History of hypersensitivity to Temsirolimus or its metabolites (including sirolimus),
polysorbate 80, or to any component of the formulation

8. Patients that are taking CYP3A4 inducers and/or inhibitors. Please see section 3.2 in
the protocol for details. If a patient has a history of taking CYP3A4 inducers and/or
inhibitors prior to enrollment on the protocol, it is strongly recommended that the
patient stops the drug and waits at least 5 half-lives of said drug before initiating
therapy on protocol.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated doses (MTDs) + Dose-limiting toxicities (DLTs)

Outcome Time Frame:

Continuous assessment throughout and determination of dose-limiting toxicities with 21 Day Cycle

Safety Issue:

Yes

Principal Investigator

Razelle Kurzrock, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2007-0668

NCT ID:

NCT00610493

Start Date:

January 2008

Completion Date:

Related Keywords:

  • Advanced Cancer
  • Advanced Cancer
  • Bevacizumab
  • Temsirolimus
  • Avastin
  • Torisel
  • CCI-779
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • dynamic contrast-enhanced magnetic resonance imaging
  • DCE
  • magnetic resonance imaging
  • MRI
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030